Key Points

A phase II clinical trial of a personalized peptide cancer vaccine for patients with platinum-based chemotherapy-resistant metastatic bladder cancer has found that the vaccine plus best supportive care resulted in significant improvement in overall survival (7.9 months vs 4.1 months with best supportive care alone), although progression-free survival was not improved.

The study results suggest that personalized peptide vaccination might be an important treatment option for advanced bladder cancer after failure of platinum-based regimens.

Further large-scale, randomized trials of a personalized peptide cancer vaccine in patients with advanced or metastatic urothelial cancer are needed to confirm this study’s results.

Although urothelial cancer of the bladder is sensitive to platinum-based chemotherapy, the vast majority of patients treated with these therapies will develop progressive disease within 8 months of treatment, and the median survival is reported to be between 13 and 15 months, according to a new study by Noguchi et al. To assess the potential of personalized peptide vaccination to improve outcomes in patients with progressive bladder cancer after first-line platinum-based chemotherapy, Masanori Noguchi, MD, PhD, Professor in the Clinical Research Division of the Kurume University Research Center for Innovative Cancer Therapy in Japan, and colleagues launched a phase II randomized clinical trial testing the cancer vaccine plus best supportive care to boost anticancer immunity. The researchers found that the combination therapy did result in significant improvement in overall survival, although progression-free survival was not improved.

The study results suggest that personalized peptide vaccination might be an important treatment option for advanced bladder cancer after failure of platinum-based regimens. The study is published in Clinical Cancer Research.

Study Methodology

The researchers enrolled 80 patients, median age of 65 years, with metastatic bladder cancer at nine medical centers in Japan between February 2010 and November 2013. The patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a life expectancy of at least 12 weeks. The primary endpoint was progression-free survival, and the secondary endpoints were overall survival, safety, and immune responses to personalized peptide vaccination.

Thirty-nine patients were randomly assigned to personalized peptide vaccination plus best supportive care, and 41 patients were randomly assigned to best supportive care alone. Best supportive care included palliative radiotherapy, antibiotics, analgesics, corticosteroids, and transfusion. Priory therapy included surgery, radiotherapy, or local bladder instillations of either chemotherapy or bacillus Calmette-Guérin, and all patients had received systemic platinum-based chemotherapy.

The administration schedule of personalized peptide vaccination plus best supportive care included 8 doses at 1-week intervals followed by 4 doses at 2-week intervals; total administration of the treatment was 12 doses. Under personalized peptide vaccination treatment, two to four peptides were selected by HLA typing and a high titer level of peptide-specific IgG to 31 candidate peptides in pretreatment serum. These 31 candidate peptides were applicable for patients with positive HLA-A2, -A3, -A11, -A24, -A26, -A31, or -A33 alleles, which cover the majority of the global population.

“We were excited to see that personalized peptide vaccination led to a significant improvement in overall survival,” said Dr. Noguchi in a statement. “This suggests that this immunotherapeutic approach might become a treatment option for advanced bladder cancer after failure of platinum-based regimens. However, large-scale, randomized clinical trials are needed to confirm our results.”

Dr. Noguchi is the corresponding author of this study. This study was funded by grants from the Program for Fostering Regional Innovation of the Ministry of Education, Science, Sports, and Culture in Japan.